Evidence map›Paper›PMID 18383343›Full record

ArticleGlia2008

H-Ras increases urokinase expression and cell invasion in genetically modified human astrocytes through Ras/Raf/MEK signaling pathway.

Yunge Zhao, Aizhen Xiao, Charles G Dipierro, Rana Abdel-Fattah, Samson Amos, Gerard T Redpath, Joan E Carpenter, Russell O Pieper, Isa M Hussaini

Abstract read
In one paragraph

Article in Glia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 21 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Yunge ZhaoDepartment of Pathology, University of Virginia, Charlottesville, Virginia 22908, USA. yz5u@virginia.edu
Aizhen Xiao
Charles G Dipierro
Rana Abdel-Fattah
Samson Amos
Gerard T Redpath
Joan E Carpenter
Russell O Pieper
Isa M Hussaini
University of Virginia · USNeurological Surgery · US

Funding

Role of PKCeta in Regulating Astrocytoma Invasive GrowthR01CA090851 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI LOPES, MARIA-BEATRIZ S. · 2002 to 2011
$2.1M
Role of LRP in Astrocytoma MigrationR01NS035122 · NINDS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI HUSSAINI, ISA M · 2003 to 2007
$1.6M
REGULATION OF LRP EXPRESSION AND FUNCTION IN THE CNSR29NS035122 · NINDS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI HUSSAINI, ISA M · 1997 to 2001
$262k
NCI NIH HHS CA90851NCI NIH HHS P30 CA44570NCI NIH HHS R01 CA090851NINDS NIH HHS NS35122NINDS NIH HHS R01 NS035122NINDS NIH HHS R29 NS035122
6 · The paper itself

Abstract

Previous study reported that the activation of Ras pathway cooperated with E6/E7-mediated inactivation of p53/pRb to transform immortalized normal human astrocytes (NHA/hTERT) into intracranial tumors strongly resembling human astrocytomas. The mechanism of how H-Ras contributes to astrocytoma formation is unclear. Using genetically modified NHA cells (E6/E7/hTERT and E6/E7/hTERT/Ras cells) as models, we investigated the mechanism of Ras-induced tumorigenesis. The overexpression of constitutively active H-RasV12 in E6/E7/hTERT cells robustly increased the levels of urokinase plasminogen activator (uPA) mRNA, protein, activity and invasive capacity of the E6/E7/hTERT/Ras cells. However, the expressions of MMP-9 and MMP-2 did not significantly change in the E6/E7/hTERT and E6/E7/hTERT/Ras cells. Furthermore, E6/E7/hTERT/Ras cells also displayed higher level of uPA activity and were more invasive than E6/E7/hTERT cells in 3D culture, and formed an intracranial tumor mass in a NOD-SCID mouse model. uPA specific inhibitor (B428) and uPA neutralizing antibody decreased uPA activity and invasion in E6/E7/hTERT/Ras cells. uPA-deficient U-1242 glioblastoma cells were less invasive in vitro and exhibited reduced tumor growth and infiltration into normal brain in xenograft mouse model. Inhibitors of Ras (FTA), Raf (Bay 54-9085) and MEK (UO126), but not of phosphatidylinositol 3-kinase (PI3K) (LY294002) and of protein kinase C (BIM) pathways, inhibited uPA activity and cell invasion. Our results suggest that H-Ras increased uPA expression and activity via the Ras/Raf/MEK signaling pathway leading to enhanced cell invasion and this may contribute to increased invasive growth properties of astrocytomas.

Indexed as

Analysis of VarianceAnimalsAstrocytesBrain NeoplasmsCells, CulturedDisease Models, AnimalGene Expression RegulationHumansMaleMiceMice, Inbred NODMice, SCIDMitogen-Activated Protein KinasesProto-Oncogene Proteins p21(ras)ras ProteinsSignal TransductionHras protein, mouseMitogen-Activated Protein KinasesProto-Oncogene Proteins p21(ras)ras ProteinsUrokinase-Type Plasminogen Activator

Identifiers

PMID18383343
PMCPMC2408768
OpenAlexW2090422031

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.